NM_000038.6(APC):c.1902T>G (p.Ser634Arg) AND Familial adenomatous polyposis 1

delete

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: May 3, 2023
Review status:: criteria provided, conflicting classifications

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV003335256.3

Allele description

NM_000038.6(APC):c.1902T>G (p.Ser634Arg)

Gene:

APC:APC regulator of WNT signaling pathway [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

5q22.2

Genomic location:

Preferred name:

NM_000038.6(APC):c.1902T>G (p.Ser634Arg)

HGVS:

NC_000005.10:g.112835109T>G
NG_008481.4:g.147589T>G
NM_000038.6:c.1902T>GMANE SELECT
NM_001127510.3:c.1902T>G
NM_001127511.3:c.1848T>G
NM_001354895.2:c.1902T>G
NM_001354896.2:c.1956T>G
NM_001354897.2:c.1932T>G
NM_001354898.2:c.1827T>G
NM_001354899.2:c.1818T>G
NM_001354900.2:c.1779T>G
NM_001354901.2:c.1725T>G
NM_001354902.2:c.1629T>G
NM_001354903.2:c.1599T>G
NM_001354904.2:c.1524T>G
NM_001354905.2:c.1422T>G
NM_001354906.2:c.1053T>G
NP_000029.2:p.Ser634Arg
NP_001120982.1:p.Ser634Arg
NP_001120983.2:p.Ser616Arg
NP_001341824.1:p.Ser634Arg
NP_001341825.1:p.Ser652Arg
NP_001341826.1:p.Ser644Arg
NP_001341827.1:p.Ser609Arg
NP_001341828.1:p.Ser606Arg
NP_001341829.1:p.Ser593Arg
NP_001341830.1:p.Ser575Arg
NP_001341831.1:p.Ser543Arg
NP_001341832.1:p.Ser533Arg
NP_001341833.1:p.Ser508Arg
NP_001341834.1:p.Ser474Arg
NP_001341835.1:p.Ser351Arg
LRG_130:g.147589T>G
NC_000005.9:g.112170806T>G
NM_000038.5:c.1902T>G

Protein change:

S351R

Links:

dbSNP: rs876659460

NCBI 1000 Genomes Browser:

rs876659460

Molecular consequence:

NM_000038.6:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127510.3:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001127511.3:c.1848T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354895.2:c.1902T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354896.2:c.1956T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354897.2:c.1932T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354898.2:c.1827T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354899.2:c.1818T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354900.2:c.1779T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354901.2:c.1725T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354902.2:c.1629T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354903.2:c.1599T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354904.2:c.1524T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354905.2:c.1422T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001354906.2:c.1053T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Familial adenomatous polyposis 1 (FAP1)
Synonyms:: POLYPOSIS, ADENOMATOUS INTESTINAL; FAMILIAL ADENOMATOUS POLYPOSIS 1, ATTENUATED; APC-Associated Polyposis Conditions
Identifiers:: MONDO: MONDO:0021056; MedGen: C2713442; OMIM: 175100

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003525740	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jan 17, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 24599579, 27696107, 28492532
SCV004044260	Myriad Genetics, Inc.	criteria provided, single submitter (Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))	Likely pathogenic (May 3, 2023)	unknown	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003525740

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jan 17, 2022)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV004044260

Myriad Genetics, Inc.

criteria provided, single submitter

(Myriad Autosomal Dominant, Autosomal Recessive and X-Linked Classification Criteria (2023))

Likely pathogenic
(May 3, 2023)

unknown

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The UMD-APC database, a model of nation-wide knowledge base: update with data from 3,581 variations.

Grandval P, Blayau M, Buisine MP, Coulet F, Maugard C, Pinson S, Remenieras A, Tinat J, Uhrhammer N, Béroud C, Olschwang S.

Hum Mutat. 2014 May;35(5):532-6. doi: 10.1002/humu.22539. Epub 2014 Apr 7.

PubMed [citation]

PMID:: 24599579

Expanding the genotype-phenotype spectrum in hereditary colorectal cancer by gene panel testing.

Rohlin A, Rambech E, Kvist A, Törngren T, Eiengård F, Lundstam U, Zagoras T, Gebre-Medhin S, Borg Å, Björk J, Nilbert M, Nordling M.

Fam Cancer. 2017 Apr;16(2):195-203. doi: 10.1007/s10689-016-9934-0.

PubMed [citation]

PMID:: 27696107
PMCID:: PMC5357488

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV003525740.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Studies have shown that this variant is associated with altered splicing, but the impact on the resulting protein product is unknown (PMID: 24599579; Invitae). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 231954). This missense change has been observed in individual(s) with clinical features of familial adenomatous polyposis (PMID: 27696107). This variant is present in population databases (no rsID available, gnomAD 0.004%). This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 634 of the APC protein (p.Ser634Arg).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Myriad Genetics, Inc., SCV004044260.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

This variant is considered likely pathogenic. mRNA analysis has demonstrated abnormal mRNA splicing occurs [Myriad internal data].

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 2, 2024

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